C. Schild-poulter et al., The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase, J BIOL CHEM, 276(20), 2001, pp. 16848-16856
The Ku antigen (70- and 80-kDa subunits) is a regulatory subunit of DNA-dep
endent protein kinase (DNA-PK) that promotes the recruitment of the catalyt
ic subunit of DNA-PK (DNA-PKcs) to DNA ends and to specific DNA sequences f
rom which the kinase is activated. Ku and DNA-PKcs plays essential roles in
double-stranded DNA break repair and V(D)J recombination and have been imp
licated in the regulation of specific gene transcription. In a yeast two-hy
brid screen of a Jurkat T cell cDNA library, we have identified a specific
interaction between the 70-kDa subunit of Ku heterodimer and the homeodomai
n of HOXC4, a homeodomain protein expressed in the hematopoietic system. Un
expectedly, a similar interaction with Ku was observed for several addition
al homeodomain proteins including octamer transcription factors 1 and 2 and
D1x2, suggesting that specific binding to Ku may be a property shared by m
any homeodomain proteins. Ku-homeodomain binding was mediated through the e
xtreme C terminus of Ku70 and was abrogated by amino acid substitutions at
Lys(595)/lys(596). Ku binding allowed the recruitment of the homeodomain to
DNA ends and dramatically enhanced the phosphorylation of homeodomain-cont
aining proteins by DNA-PK. These results suggest that Ku functions as a sub
strate docking protein for signaling by DNA-PK to homeodomain proteins from
DNA ends.